Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells

Abstract

BackgroundIn contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood.ResultsHere, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2+ cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2+ cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages.ConclusionsSox2+ cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2+ cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection.

Sox2 haploinsufficiency primes regeneration and Wnt responsiveness in the mouse cochlea

“…Complete and partial Sox2 deficiencies cause multiorgan defects including anophthalmia, epilepsy, and trachea-esophageal, cochlear, and genital anomalies in mice and humans (10,11,(17)(18)(19)(20). Moreover, some regenerating tissues are sensitive to Sox2 dosage and are dependent on Sox2 activation (10,17,27). Our study shows that Sox2 haploinsufficiency allows essentially normal development of the cochlea.…”

“…For example, Sox2 loss of function impairs adult neurogenesis and tracheal repair (16,(24)(25)(26). Moreover, Sox2 is upregulated during spinal cord regeneration, with damage inducing the proliferation of Sox2 + cells, and inhibition of Sox2 limiting their regeneration in a dose-dependent manner (27). Thus, the prevailing notion is that Sox2 insufficiency impairs both the development and regeneration of tissues.…”

Accelerated cell divisions drive the outgrowth of the regenerating spinal cord in axolotls

“…In zebrafish (Hui et al, 2010(Hui et al, , 2015, Xenopus (Gaete et al, 2012), mouse (Lacroix et al, 2014) and axolotl (this work, Rodrigo Albors et al, 2015;Holtzer, 1956) traumatic spinal cord injury triggers a long-range wave of increased cell proliferation. It is however clear that although the potential to replace lost cells or tissue exists in other species, they are not as efficient as axolotls at resolving spinal cord injuries.…”

Neuronal Regeneration from Ependymo-Radial Glial Cells: Cook, Little Pot, Cook!

“…sox2 is also important for spinal cord regeneration in larval Xenopus (Gaete et al, 2012) and lesion-induced ERG proliferation in the adult lesioned zebrafish spinal cord (Ogai et al, 2014).…”